2-Methylpiperidine → 5-Bromo-2-(2-methylpiperidin-1-YL)benzaldehyde

HRID 1630967

Reaction equation

[CH3:1][CH:2]1[CH2:7][CH2:6][CH2:5][CH2:4][NH:3]1.C(=O)([O-])[O-].[Na+].[Na+].[Br:14][C:15]1[CH:16]=[CH:17][C:18](F)=[C:19]([CH:22]=1)[CH:20]=[O:21]>CS(C)=O.O>[Br:14][C:15]1[CH:16]=[CH:17][C:18]([N:3]2[CH2:4][CH2:5][CH2:6][CH2:7][CH:2]2[CH3:1])=[C:19]([CH:22]=1)[CH:20]=[O:21]

Participants

Conditions

Temperature: 120 °C

Procedure

2-Methylpiperidine (15.4 mL, 130.0 mmol) and anhydrous sodium carbonate (13.8 g, 130.0 mmol) were added into a solution of 5-bromo-2-fluorobenzaldehyde (13.2 g, 65.0 mmol) in DMSO (160 mL) and water (40 mL). The resulting mixture was heated at 120° C. for 16 hours. The reaction mixture was diluted with water (1 L) and extracted with Et2O (2×750 mL). The organic layers were washed with brine (500 mL, pH 5-6 adjusted with a 5N aqueous solution of HCl), combined and dried (MgSO4). The solvents were removed under reduced pressure to give the title compound as a brown yellow oil (16.3 g, 89%) used without further purification in the next step. HPLC (Method A), Rt 2.20 min (purity: 93.7%). UPLC/MS, M+(ESI): 282.1, 284.1. 1H NMR (CDCl3, 300 MHz) δ 10.40 (s, 1H), 7.93 (d, J=2.5 Hz, 1H), 7.62 (dd, J=8.6, 2.5 Hz, 1H), 7.12 (d, J=8.6 Hz, 1H), 3.17 (m, 1H), 3.06 (m, 1H), 2.81 (ddd, J=11.7, 7.6, 3.9 Hz, 1H), 1.89 (m, 1H), 1.83-1.65 (m, 3H), 1.58-1.42 (m, 2H), 0.91 (d, J=6.3 Hz, 3H).

Workup

extractionextracted with Et2O (2×750 mL)
washThe organic layers were washed with brine (500 mL, pH 5-6
dry with materialdried (MgSO4)
customThe solvents were removed under reduced pressure

Sources & evidence

ORD record: ord-50941ea59dac4bbf84436330ffc33905
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08791142B2

Linked notes

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